We found some spontaneous fusion between tumor cells and host derived cells in vivo within the mouse Ehrlich ascites tumor (EAT), occurring slowly as a part of fusion amongst various cell types. The tumor-host cell hybrids lose some chromosomes and grow as malignant cells. Incidence of such cells slowly increases in an EAT when transferred into and maintained intraperitoneally in a different host strain even in the absence of an immunoselective pressure. This process seems to account for antigenic changes on the tumor cell surface. For example, EAT transferred intraperitoneally from a parental strain mouse into an F1 hybrid strain gradually loses its subcutaneous tumorigenicity for the parental strain with increasing number of intraperitoneal passages within the F1 strain, but remains tumorigenic by the subcutaneous route for the F1 strain. This indicates acquisition of host histocompatibility components by tumor cells. However, using an indirect immunolabeling technique we have failed to uncover any strong expression of host H-2 antigens by the EAT cells in radioautographic preparations. This is complicated by the fact that all H-2 isoantisera show non H-2 related binding with tumor cells because of the presence of antibodies directed against MuLV antigens. Following removal of such antibodies by appropriate absorption, we shall test whether EAT cells can bind the antisera when grown subcutaneously, or when treated with various surface-altering agents (trypsin, neuroaminidase, sodium periodate and sodium iodoacetate). We shall also test these cells for their ability to bind and be agglutinated by various lectins (PHA, ConA, wheat germ agglutinin and soybean agglutinin) as possible indicators of cell surface alterations because of tumor-host cell fusion. A large fraction of the host lymphocytes invading Ehrlich ascites tumor or TA-3 (St) solid tumors as well as those appearing in host spleens appear to lack in surface IgM or theta antigen. We shall examine these "double negative" cells for their functional potentials and possible presence of other surface receptors (viz. C'3 and Fc). BIBLIOGRAPHIC REFERENCE: L. Kaizer and P.K. Lala. Post-mitotic age of host mononuclear cells migrating into TA-3(St) solid tumors. Cell Tissue Kinet. Vol. 10, 1977 in press.